As pharmaceutical and biotechnology companies increase their investment in immuno-oncology programs to facilitate rapid development of novel immunotherapies, there is increasing pressure to discover and validate relevant biomarkers. Cambridge Healthtech Institute’s Third Annual Immuno-Oncology Biomarkers 1: Predictive Biomarkers and Companion Diagnostics meeting will bring together biomarkers experts from industry and academia to address rapid development of predictive and prognostic IO biomarkers, utility of these biomarkers in clinical trials, and their potential as companion diagnostics.

Final Agenda

Sunday, June 10

4:30-6:30 pm Short Course and Conference Registration

5:00-8:30 Dinner Short Course*

SC1: Fit-for-Purpose Biomarker Assay Development and Validation

*Separate registration required

Monday, June 11

7:00 am Conference Registration and Morning Coffee

8:00 Organizer’s Welcome

OPENING PLENARY SESSION: EMERGING APPROACHES FOR CANCER

8:05 Chairperson’s Opening Remarks

George A. Green, IV, PhD, Head, Pharmacodiagnostics, Bristol-Myers Squibb

8:10 Clinical Genomic Profiling Using the MSK-IMPACT™ Large Panel NGS Assay to Guide Patient Selection for Targeted and Immune Therapies

Marc Ladanyi, MD, William J. Ruane Chair in Molecular Oncology, Molecular Diagnostics Service and Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center

As the centerpiece of an institutional initiative in clinical cancer genomics, we have implemented large scale genomic profiling for targetable cancer drivers and other cancer-relevant alterations in all patients with advanced solid cancers. Since 2014, over 23,000 patients have been profiled using the MSK-IMPACT™ targeted large panel, capture-based DNAseq assay. MSK-IMPACT™, which received FDA clearance in 2017, allows robust detection of somatic mutations in all known cancer genes, copy number changes and select cancer fusion gene rearrangements, as well as assessing overall tumor mutation burden and microsatellite instability. Patients are also screened for oncogenic fusions by targeted RNAseq and for germline cancer predisposition alleles and evidence of clonal hematopoiesis.

8:40 Widgets to Cancer Patient-Specific Digits: The Case for Out-of-Clinic Objective Measures and Their Potential Impact to Remote Patient Monitoring in Precision Oncology and Discovery

Christopher M. Hartshorn, PhD, Program Director, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health

Albeit the case for long-term, out-of-clinic monitoring has been obvious for many chronic diseases, the case for cancer has not been as clear. The National Cancer Institute has begun piloting and funding various aspects to enable an Internet of Cancer Medical Things. This talk will focus on these efforts currently and prospectively as well as the overall vision to coordinate a much broader initiative to improve our understanding of cancer progression and improve the delivery of cancer care.

9:10 Coffee Break in the Exhibit Hall with Poster Viewing

PATIENT SELECTION BIOMARKERS AND COMPANION DIAGNOSTICS IN IMMUNO-ONCOLOGY

9:55 Chairperson’s Remarks

Shirin Khambata Ford, PhD, Global Head, Biomarkers and Diagnostics, Executive Director, Oncology Global Medical Affairs, Merck

10:00 Patient Selection Strategies for Making Precision Medicine a Reality for Immuno-Oncology

Shirin Khambata Ford, PhD, Global Head, Biomarkers and Diagnostics, Executive Director, Oncology Global Medical Affairs, Merck

This talk will highlight the development and implementation of the PD-L1 IHC testing globally to select patients for pembrolizumab treatment across different tumor types. It will also focus on some of the more recent biomarker approaches that are being utilized to optimally select patients who will benefit from anti-PD1 therapies such as microsatellite instability/mismatch repair deficiency assessment and tumor mutation burden.

10:30 Transitioning from Exploratory Tumor Mutation Burden Assays to IVD Platforms for Immuno-Oncology

George A. Green, IV, PhD, Head, Pharmacodiagnostics, Bristol-Myers Squibb

A range of methods exist for measuring tumor mutation burden (TMB), including whole exome sequencing (WES) and genomic profiling assays (e.g. FoundationOne®). While WES is used in research, more efficient methods, such as FoundationOne®, are being assessed for clinical use. Therefore, harmonization of various tests will be essential to establish diagnostics. This discussion will expand on previous data demonstrating concordance between WES and FoundationOne® in pursuit of an IVD assessing TMB.

11:00 Differential Response of Target Germline Variation Reveals Patient Enrichment Strategy for a Novel Cancer Immunotherapy

Mingjie Liu, PhD, Clinical Biomarker Lead, Translational Science, Oncology Business Group, Eisai

In the discovery and development of cancer immunotherapy, the polymorphic nature of immune therapeutic targets and limited translatability of mouse models make prediction of human response to an immunotherapy challenging. In this presentation, we will discuss an application of human germline genetics and primary human tumor tissues for the characterization and translational biomarker discovery of a novel drug candidate.

11:30 CO-PRESENTATION: Proteomic Profiling of Biomarkers for Response to Immunotherapy in Melanoma Patients Using Proximity Extension Assay

Ida Grundberg, PhD, Business Development Manager, Sales, Olink Proteomics

Marijana Rucevic, PhD, Business Development Manager, Sales, Olink Proteomics

Checkpoint immunotherapy has greatly improved clinical outcomes in the subset of melanoma patients which urges a need to develop biomarkers for therapy response. Olink’s Proximity Extension Assay was applied to profile around 1,000 validated plasma proteins in 58 melanoma patients treated with anti-PD-1 or anti-PDL-1 (44 responders and 14 non-responders). Results demonstrate significant changes in around 100 protein biomarkers over the course of treatment and six proteins were identified as potential markers of therapy response.

12:00 pm Luncheon Presentation: Validation of an RNA-Based Immune Profiling Assay for Limiting & Diverse Patient Samples

Natalie LaFranzo, Director, Scientific Projects and Market Development, Cofactor Genomics

The success of immunotherapy development relies on robust approaches for characterizing and interpreting a patient’s immune system; specifically, the microenvironment surrounding a tumor. Using RNA-seq and machine-learning informatics, Cofactor’s Paragon assay overcomes current challenges associated with commonly used methods, even for limiting and degraded samples. Complex molecular signals are measured and reported in an easy to interpret report. Case study data with control samples and patient materials will be discussed.

BIOMARKERS TO PREDICT RESPONSE TO IMMUNOTHERAPY

1:25 Chairperson’s Remarks

David L. Rimm, MD, PhD, Professor, Pathology, Yale University

1:30 Immunophenotyping to Differentiate Responder and Non-Responder Patients in Cancer Immunotherapy

George Poste, DVM, PhD, Chief Scientist, Complex Adaptive Systems, Regents’ Professor and Del E. Webb Chair in Health Innovation, Arizona State University

The clinical benefits of immune checkpoint inhibitors in a variety of malignancies are unprecedented. Unfortunately, the level of positive therapeutic response is not consistent across different tumor classes and even in responsive tumor lineages non-responders still dominate. The need for comprehensive immunophenotyping to identify the mechanisms underlying these differential responses and better predict responder patients is an urgent clinical and economic imperative.

2:00 Dual Biomarker Strategy to Understand Novel Translational Biomarkers to Stratify Patients Effectively for Personalized Cancer Immunotherapy

Jianda Yuan, MD, PhD, Senior Director, Translational Oncology, Early Clinical Oncology Development, Merck Research Labs

Immune checkpoint blockade therapies are revolutionizing the standard cancer treatment. Despite the current success of these therapies, not all patients respond to immunotherapy, and even those that do often experience toxicities. Combination approaches are the keys to improving clinical response. High throughput next-generation sequencing technologies enable us to explore the mechanisms of responses as well as resistance. Emerging dual biomarkers (tumor mutational burden and gene expression profile) allow us to understand novel translational biomarkers to stratify patients effectively for personalized cancer immunotherapy.

2:30 Predicting Response to Immunotherapy: PD-L1 and Beyond

David L. Rimm, MD, PhD, Professor, Pathology, Yale University

Prediction of response to PD-1 axis drugs began with simple IHC-based assessment of PD-L1 with different assays matched to different drugs. More recently, assessment of DNA MMR has gained its first approval as a predictive assay. This presentation will discuss these tests and future more sophisticated tests for protein, including expression in the microenvironment and the tumor, mRNA, as expression signatures, and DNA, including tumor mutational burden.

3:00 Mitigating Risk when Navigating the Journey from Biomarker Assay Validation to the Commercial Deployment of a CDx

Cindy Spittle, PhD, Vice President, Development and Scientific Affairs, MolecularMD

Multiple biomarker assays and methodologies are being explored for use in I/O studies. Examples of methods currently being used for MSI, TMB and gene expression analysis will be reviewed. Insights regarding the technical, regulatory and operational factors that should be evaluated when selecting an assay for implementation in a clinical trial and co-development as a complementary or companion diagnostic will be discussed.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:10 Chairperson’s Remarks

David L. Rimm, MD, PhD, Professor, Pathology, Yale University

4:15Characterization of the Soluble HLA Peptidome for Predicting Response to Immunotherapy

Tim Fugmann, PhD, Head, Precision Medicine, Philochem AG

4:45 The Genomic and Immunologic Determinants of Response to Cancer Immunotherapy

Rajarsi Mandal, MD, Head and Neck Surgical Oncology Fellow, Memorial Sloan Kettering Cancer Center

Immune checkpoint blockade is a promising approach for the treatment of human malignancies and has led to improved response rates and durable clinical benefit in a subset of patients. However, the extent to which patients derive benefit is diverse and the determinants of response to therapy are ill-defined. We have sought to define the genomic and immunologic determinants of response to immune checkpoint blockade therapies such as anti-CTLA-4 and anti-PD-1. Our work has shown that tumor mutational burden, clonality, and the tumor immune landscape help dictate clinical response to immune-based therapies.

5:15 Tumor Microenvironment as Biomarker for Immunotherapy

Kien Thiam Tan, PhD, Vice Director, Medical Informatics, ACT Genomics

The success of immune checkpoint inhibitors in a subset of cancer patients has led to major efforts in identifying predictive biomarkers. In addition to PD-L1 staining and tumor mutational burden, factors such as immune cell compositions and checkpoint molecule profiles, antigen presenting machinery and immune resistance signals, should also be considered when evaluating a patient for immunotherapy. In this talk, a novel chip-based assay to monitor tumor microenvironment using FFPE tissue will be presented.

5:45 Welcome Reception in the Exhibit Hall with Poster Viewing

Tuesday, June 12

7:25 am Interactive Breakout Discussion Groups with Continental Breakfast

This session features discussion groups that are led by a moderator who ensures focused conversations around the key issues listed. Attendees choose to join a specific group, and the small, informal setting facilitates sharing of ideas and active networking. Details on the topics and moderators are available on the conference website.

LIQUID BIOPSY FOR IMMUNO-ONCOLOGY

8:25 Chairperson’s Remarks

Theresa L. Whiteside, PhD, Professor, Pathology, Immunology and Otolaryngology, University of Pittsburgh Cancer Institute

8:30 Tumor-Derived Exosomes as Potential Biomarkers of Cancer Progression and Immune Dysfunction in Cancer

Theresa L. Whiteside, PhD, Professor, Pathology, Immunology and Otolaryngology, University of Pittsburgh Cancer Institute

Plasma-derived exosomes are emerging as promising non-invasive correlates of cancer progression. In patients with solid tumors or hematological malignancies, plasma exosomes carry a cargo enriched in immunosuppressive proteins. As immune suppression is one of the hallmarks of cancer progression, circulating exosomes rich in inhibitory molecules are implicated in mediating systemic immune suppression.

9:00 Profiling the Tumor Immune Microenvironment by Means of Liquid Biopsy

Samir Hanash, MD, PhD, Director, McCombs Institute for Cancer Early Detection and Treatment, MD Anderson Cancer Center

Interest in liquid biopsy has largely focused on ctDNA. However, plasma has a rich content in cells, extra-cellular vesicles and biomolecules that inform about tumor features, the microenvironment and the status of the immune response. Progress in defining the tumor microenvironment in solid tumors by means of liquid biopsy will be presented.

9:30 Clinical Applications of cfDNA for Targeted and Immune Therapies

Rebecca Leary, PhD, Lab Head, Next Generation Diagnostics, Novartis Institutes for BioMedical Research

Circulating tumor DNA (ctDNA) provides an opportunity for non-invasive assessment of tumor genotype, and may enable rational use of targeted and/or immune modulating therapies at several clinical milestones. Implementation of ctDNA-based assays across clinical and research settings highlights important assay characteristics and suggests future clinical applications.

10:00 Molecular Analysis of an Adaptive T Cell Response against an IL-12 Adjuvanted Vaccine: From Molecule to Mechanism

Wyatt McDonnell, Graduate Fellow, Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine

The cytokine IL-12 is known to enhance the function and quality of cytotoxic T lymphocytes (CTLs) against antigens, especially in the context of vaccines. In this study, we analyzed samples from the HIV Vaccine Trial Network (HVTN) study 087. We report the enhancement of the cellular response in individuals receiving IL-12 and identify several potential markers of successful IL-12 adjuvanted vaccination.

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

TUMOR NEOANTIGENS AS BIOMARKERS AND TARGETS

11:10 Chairperson’s Remarks

Fred Ramsdell, PhD, Vice President, Research, Parker Institute for Cancer Immunotherapy

11:15 Neoantigens and Their Relationship to Mutational Load, Mismatch Repair and Immune Checkpoint Expression

Arnold B. Gelb, MD, Senior Director, Clinical Development, Ziopharm Oncology

The objectives of this presentation are 1) to review the biological background by which somatic mutations can lead to the generation of private, highly immunogenic tumor antigens (neoantigens), 2) discuss association of neoantigens with mutational burden, mismatch repair and immune checkpoint expression, and 3) to provide an outlook on clinical applications involving assessment of neoantigens and mutational load with regards to response to immune-checkpoint blockade in solid tumors.

11:45 Tumor Neoantigen Selection Alliance (TESLA): Towards Personalized Cancer Vaccines

Fred Ramsdell, PhD, Vice President, Research, Parker Institute for Cancer Immunotherapy

It is now accepted that mutation-derived neoantigens can elicit a tumor-specific immune response. Identifying neoantigens accurately from the exome sequence is a key parameter for the development of such responses and remains a significant variable of the overall process. TESLA is a consortium-based approach involving over 30 groups to identify key parameters in neoantigen prediction. An update on the progress of the program will be discussed.

12:15 pm Driving CD8+ T Cell Responses to Mutational Neoantigens in Tumors - Harnessing Immunogenic Viral Vectors in Combination with Immune Checkpoint Modulators

Karin Jooss, PhD, CSO, Gritstone Oncology

DNA damage may cause mutations in tumors that can generate new antigens, known as tumor-specific neo-antigens (TSNAs). Accurate prediction of TSNAs is key to generate potent TSNA specific vaccine approaches. Viral vector-based vaccine platforms have shown to induce hi-titer, polyfunctional and durable CD4+ and CD8+ T-cell responses in humans. The personalized vaccine is delivered in combination with immune checkpoint blockade, to keep TSNA-induced T-cells active in the immunosuppressive tumor microenvironment.

12:45 Session Break

12:55 Luncheon Presentation: Diagnostic Solutions for Multi-Arm I-O Clinical Trials

Steven Walker, PhD, Head, Internal Product Management, Almac Diagnostics

During this talk participants will learn about Almac Diagnostics’: - Novel strategy for patient stratification in Basket & Umbrella trials - Solution to enable multiple biomarkers to be evaluated from one sample - Cancer panel solutions for both DNA & RNA - Unique product offering for Immuno-Oncology - Customised patient reporting enabling simple interpretation of molecular data.

1:25 Close of Conference